The effects of age on the dopamine (DA) turnover and 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a cofactor for monooxygenases, were investigated in the striatum and midbrain of the senescence accelerated mouse (SAM) at 6,12 and 15 months old. 6R-BH4 and DA levels were decreased significantly in the striatum of 15-month-old SAM-P/1 (senescence accelerated prone) mice. At 12 months old, DA level was decreased significantly in the striatum of SAM-P/1 compared with SAM-R/1 (senescence accelerated resistant) mice. The reduction of striatal DA level was shown to be related to the depletion of 6R-BH4 in the striatum during the processes of aging. Age-related decreases in striatal dopamine function occurred in SAM-P/1 mice earlier than in the SAM-R/1 mice. The striatal [DOPAC]/[DA] ratio, as the index of DA turnover, was increased significantly in the 15-month-old SAM-P/1 mice. On the other hand, the DA, 6R-BH4 levels and the ratio of [DOPAC]/[DA] did not show any changes in the midbrain of SAM-P/1 and SAM-R/1 during the processes of aging. It was suggested that brain vulnerability with aging may be associated with the levels of 6R-BH4.